Jim Wells, Ph.D., divisions of Developmental Biology and Endocrinology at Cincinnati Children's Hospital Medical Center, explains how the first-time molecular generation of 3-D human gastric organoids (hGOs) presents new opportunities for drug discovery, modeling early stages of stomach cancer and studying some of the underpinnings of obesity related diabetes. (Cincinnati Children's Hospital Medical Center)

Scientists have used human stem cells to create functional, 3-D stomach tissue -- in effect, little miniature versions of the organ in its earliest stages of development. This is a first, and the grown tissue will allow researchers to better study illnesses of the stomach, like those that cause ulcers and even cancer. The tissue may even be used as a treatment in and of itself by way of tiny grated patches that would grow over ulcerated stomachs.

These mini-stomachs (or gastric organoids) are reported in a study published Wednesday in Nature. They're not exactly tiny versions of the organ that digests your food, but they're a big step in the right direction.

In fact, the organoid is basically like a stomach you'd find in a very developed fetus, or perhaps in a newborn baby. It's not quite fully developed.

"It's not too far off to call it a miniature stomach," said lead author James Wells, a scientist in the divisions of Developmental Biology and Endocrinology at Cincinnati Children's Hospital Medical Center. "They're small, football shaped, hollow spheres about the size of a pea. And on the inside, they have a proper stomach lining."

That's the key element to the study's success: Inside, the organoids are lined with the folds characteristic of a stomach's lining. And when Wells and his team look closer, they can see that the very cells themselves have arranged themselves in a similar way to those in a stomachs lining.

"They kind of know what they're supposed to do," Wells said.

The researchers were able to coax the non-specific stem cells into growing into stomach tissue by mimicking the step-by-step development they'd studied in embryos. When Wells and his colleagues compared the side-by-side development of their artificial organoids and some actual mouse stomachs, they found them to grow similarly.

"Whatever the mouse stomach did at any given stage, our mini-stomach did as well, and at basically the same time, and it developed into a strikingly stomach-like architecture."

Those stomach-like organoids grow from stem cells in around a month, but they don't get past an embryonic stage of development.

"That's really just the physical limitation of growing something in a petri dish. You can put it in a bigger dish, but it's not a goldfish -- it won't just keep getting bigger," Wells said. Because the dishes lack a blood supply, the organoid is limited to a certain size by its lack of oxygen and nutrients. Wells may be able to make a more advanced stomach by creating an artificial vasculature system to grow them in. Until then, the notion of a lab-grown stomach replacement remains far-fetched.

Wells believes that the technique could be used more immediately -- within five years or so -- to create "patches" of tissue to repair ulcers and other stomach damage, he said.


The organoid (green) infected with H. pylori (red). (Kyle McCracken)

Those patches may find even better uses: James Goldenring, a professor of surgery and developmental biology at Vanderbilt University who wasn't involved in the Nature study, pointed out that these kinds of cells might be put to better use in the intestine or colon.

"Our stomachs actually heal really fast and well if they're allowed to," Goldenring said, "So I'm not sure we're going to be throwing these organoids into patients with ulcers. But that doesn't detract from the idea that this type of technology, this idea of building epithelium and using them to repair and fix things. That's a more general concept, and it's quite attractive."

And the organoids do have one immediate use. They're proving to be excellent models to study stomach illness.

When Wells and his team injected one of their mini-stomachs with H. pylori bacteria --which can cause serious ulcers that often preclude stomach cancer -- the bacteria reacted and duplicated as if it was in a real stomach. Wells hopes that the model can be used to study a wide range of human illnesses.

Calvin Kuo, a Stanford University professor of medicine and chemical and systems biology who wasn't involved with the study, agreed that the disease model had promise. "Researchers can now create personalized 'disease in a dish' models, in which diseases of the stomach can be replicated in a petri dish with the patient's own cells," he said.